tbuckley/cabot-search huggingface dataset:
Weight regain does not eliminate the long term benefits of weight management programmes
Authors: Helen Saul, Brendan Deeney, Jemma Kwint, Paul Aveyard
Journal: BMJ (2023)

The study Hartmann-Boyce J, Theodoulou A, Oke JL, et al. Long term effect of weight regain following behavioral weight management programs on cardiometabolic disease incidence and risk: systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2023;16:263-76. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/weight-regain-does-not-eliminate-the-long-term-benefits-of-weight-management-programmes/#:~:text=Study%20author&amp;text=Many%20people%20believe%20that%20if,been%20the%20case%20without%20it .
Targeting the TCA cycle through cuproptosis confers synthetic lethality on ARID1A-deficient hepatocellular carcinoma
Authors: Tao Xing, Li Li, Yiran Chen, Gaoda Ju, Guilan Li, Xiaoyun Zhu, Yubo Ren, Jing Zhao, Zhilei Cheng, Yan Li, Da Xu, Jun Liang
Journal: Cell Reports Medicine (2023)

ARID1A is among the most commonly mutated tumor suppressor genes in hepatocellular carcinoma (HCC). In this study, we conduct a CRISPR-Cas9 synthetic lethality screen using ARID1A-deficient HCC cells to identify approaches to treat HCC patients harboring ARID1A deficiency. This strategy reveals that the survival of these ARID1A-deficient HCC cells is highly dependent on genes related to the tricarboxylic acid (TCA) cycle. Mechanistically, ARID1A loss represses expression of key glycolysis-related gene PKM, shifting cellular glucose metabolism from aerobic glycolysis to dependence on the TCA cycle and oxidative phosphorylation. Cuproptosis is a recently defined form of copper-induced cell death reported to directly target the TCA cycle. Here, we find that ARID1A-deficient HCC cells and xenograft tumors are highly sensitive to copper treatment. Together, these results offer evidence of the synthetic lethality between ARID1A deficiency and mitochondrial respiration impairment, suggesting that copper treatment constitutes a promising therapeutic strategy for selectively targeting ARID1A-deficient HCC.
<i>Vital Signs</i>: Missed Opportunities for Preventing Congenital Syphilis — United States, 2022
Authors: Robert McDonald, Kevin O'Callaghan, Elizabeth Torrone, Lindley Barbee, Jeremy Grey, David Jackson, Kate Woodworth, Emily Olsen, Jennifer Ludovic, Nikki Mayes, Sherry Chen, Rachel Wingard, Michelle Johnson Jones, Fanta Drame, Laura Bachmann, Raul Romaguera, Leandro Mena
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Congenital syphilis cases in the United States increased 755% during 2012-2021. Syphilis during pregnancy can lead to stillbirth, miscarriage, infant death, and maternal and infant morbidity; these outcomes can be prevented through appropriate screening and treatment.A cascading framework was used to identify and classify missed opportunities to prevent congenital syphilis among cases reported to CDC in 2022 through the National Notifiable Diseases Surveillance System. Data on testing and treatment during pregnancy and clinical manifestations present in the newborn were used to identify missed opportunities to prevent congenital syphilis.In 2022, a total of 3,761 cases of congenital syphilis in the United States were reported to CDC, including 231 (6%) stillbirths and 51 (1%) infant deaths. Lack of timely testing and adequate treatment during pregnancy contributed to 88% of cases of congenital syphilis. Testing and treatment gaps were present in the majority of cases across all races, ethnicities, and U.S. Census Bureau regions.Addressing missed opportunities for prevention, primarily timely testing and appropriate treatment of syphilis during pregnancy, is important for reversing congenital syphilis trends in the United States. Implementing tailored strategies addressing missed opportunities at the local and national levels could substantially reduce congenital syphilis.
Glucose Deprivation Promotes Pseudohypoxia and Dedifferentiation in Lung Adenocarcinoma
Authors: Pasquale Saggese, Aparamita Pandey, Martín Alcaraz, Eileen Fung, Abbie Hall, Jane Yanagawa, Erika F. Rodriguez, Tristan R. Grogan, Giorgio Giurato, Giovanni Nassa, Annamaria Salvati, Orian S. Shirihai, Alessandro Weisz, Steven M. Dubinett, Claudio Scafoglio
Journal: Cancer Research (2023)

Abstract Increased utilization of glucose is a hallmark of cancer. Sodium-glucose transporter 2 (SGLT2) is a critical player in glucose uptake in early-stage and well-differentiated lung adenocarcinoma (LUAD). SGLT2 inhibitors, which are FDA approved for diabetes, heart failure, and kidney disease, have been shown to significantly delay LUAD development and prolong survival in murine models and in retrospective studies in diabetic patients, suggesting that they may be repurposed for lung cancer. Despite the antitumor effects of SGLT2 inhibition, tumors eventually escape treatment. Here, we studied the mechanisms of resistance to glucose metabolism-targeting treatments. Glucose restriction in LUAD and other tumors induced cancer cell dedifferentiation, leading to a more aggressive phenotype. Glucose deprivation caused a reduction in alpha-ketoglutarate (αKG), leading to attenuated activity of αKG-dependent histone demethylases and histone hypermethylation. The dedifferentiated phenotype depended on unbalanced EZH2 activity that suppressed prolyl-hydroxylase PHD3 and increased expression of hypoxia-inducible factor 1α (HIF1α), triggering epithelial-to-mesenchymal transition. Finally, a HIF1α-dependent transcriptional signature of genes upregulated by low glucose correlated with prognosis in human LUAD. Overall, this study furthers current knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to glucose deprivation and identifying targets to prevent the development of resistance to therapies targeting glucose metabolism. Significance: Epigenetic adaptation allows cancer cells to overcome the tumor-suppressive effects of glucose restriction by inducing dedifferentiation and an aggressive phenotype, which could help design better metabolic treatments.
Author Correction: Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture
Authors: Jennifer R S Meadows, Jefrey M Kidd, Guo-Dong Wang, Heidi G Parker, Peter Z Schall, Matteo Bianchi, Matthew J Christmas, Katia Bougiouri, Reuben M Buckley, Christophe Hitte, Anthony K Nguyen, Chao Wang, Vidhya Jagannathan, Julia E Niskanen, Laurent A F Frantz, Meharji Arumilli, Sruthi Hundi, Kerstin Lindblad-Toh, Catarina Ginja, Kadek Karang Agustina, Catherine André, Adam R Boyko, Brian W Davis, Michaela Drögemüller, Xin-Yao Feng, Konstantinos Gkagkavouzis, Giorgos Iliopoulos, Alexander C Harris, Marjo K Hytönen, Daniela C Kalthof, Yan-Hu Liu, Petros Lymberakis, Nikolaos Poulakakis, Ana Elisabete Pires, Fernando Racimo, Fabian Ramos-Almodovar, Peter Savolainen, Semina Venetsani, Imke Tammen, Alexandros Triantafyllidis, Bridgett vonHoldt, Robert K Wayne, Greger Larson, Frank W Nicholas, Hannes Lohi, Tosso Leeb, Ya-Ping Zhang, Elaine A Ostrander
Journal: Genome biology (2023)
Magnetic chitin beads (MCB) coated with <i>Vibrio cholerae</i> reveals transcriptome dynamics in adult mice with a complex gut microbiota
Authors: Zi-Xin Qin, Guo-Zhong Chen, Wei Bao, Yao Ma, Xiao-Man Yang, Chun-Rong Yi, Mei Luo, Jun Hu, Zhi Liu
Journal: Gut Microbes (2023)

Vibrio cholerae adapts to the host environment by altering gene expression. Because of the complexity of the gut microbiome, current in vivo V. cholerae transcriptome studies have focused on microbiota-undeveloped conditions, neglecting the interaction between the host's commensal gut microbiota and V. cholerae. In this study, we analyzed the transcriptome of fully colonized adult mice in vivo using V. cholerae coated-magnetic chitin beads (vcMCB). This provides a simple yet powerful method for obtaining high-quality RNA from V. cholerae during colonization in mice. The transcriptome of V. cholerae recovered from adult mice infected with vcMCB shows differential expression of several genes when compared to V. cholerae recovered from the infant mouse and infant rabbit model. Some of these genes were also observed to be differentially expressed in previous studies of V. cholera recovered from human infection when compared to V. cholerae grown in vitro. In particular, we confirmed that V. cholerae resists the inhibitory effects of low pH and formic acid from gut microbiota, such as Anaerostipes caccae and Dorea formicigenerans, by downregulating vc1080. We propose that the vc1080 product may protect V. cholerae from formic acid stress through a novel acid tolerance response mechanism. Transcriptomic data obtained using the vcMCB system provide new perspectives on the interaction between V. cholerae and the gut microbiota, and this approach can also be applied to studies of other pathogenic bacteria.
<i>SUV39H1</i> Ablation Enhances Long-term CAR T Function in Solid Tumors
Authors: Sheila López-Cobo, Jaime R. Fuentealba, Paul Gueguen, Pierre-Emmanuel Bonté, Kyriaki Tsalkitzi, Irena Chacón, Salomé Glauzy, Armelle Bohineust, Ariane Biquand, Lisseth Silva, Zelia Gouveia, Christel Goudot, Franck Perez, Michael Saitakis, Sebastian Amigorena
Journal: Cancer Discovery (2023)

Abstract Failure of adoptive T-cell therapies in patients with cancer is linked to limited T-cell expansion and persistence, even in memory-prone 41BB-(BBz)–based chimeric antigen receptor (CAR) T cells. We show here that BBz-CAR T-cell stem/memory differentiation and persistence can be enhanced through epigenetic manipulation of the histone 3 lysine 9 trimethylation (H3K9me3) pathway. Inactivation of the H3K9 trimethyltransferase SUV39H1 enhances BBz-CAR T cell long-term persistence, protecting mice against tumor relapses and rechallenges in lung and disseminated solid tumor models up to several months after CAR T-cell infusion. Single-cell transcriptomic (single-cell RNA sequencing) and chromatin opening (single-cell assay for transposase accessible chromatin) analyses of tumor-infiltrating CAR T cells show early reprogramming into self-renewing, stemlike populations with decreased expression of dysfunction genes in all T-cell subpopulations. Therefore, epigenetic manipulation of H3K9 methylation by SUV39H1 optimizes the long-term functional persistence of BBz-CAR T cells, limiting relapses, and providing protection against tumor rechallenges. Significance: Limited CAR T-cell expansion and persistence hinders therapeutic responses in solid cancer patients. We show that targeting SUV39H1 histone methyltransferase enhances 41BB-based CAR T-cell long-term protection against tumor relapses and rechallenges by increasing stemness/memory differentiation. This opens a safe path to enhancing adoptive cell therapies for solid tumors. See related article by Jain et al., p. 142. This article is featured in Selected Articles from This Issue, p. 5
Abstract 12159: Heart Generation via Blastocyst Complementation in Mesp1/2-Deficient Mice
Authors: Yuto Abe, Taketaro Sadahiro, Ryo Fujita, Yu Yamada, tatsuya akiyama, Koji Nakano, Seiichiro Honda, Yoko Tanimoto, Hayate Suzuki, Seiya Mizuno, Satoru Takahashi, Tomoyuki Yamaguchi, Hideki Masaki, Kosuke Hattori, Tomoji Mashimo, Masaki Ieda
Journal: Circulation (2023)

Introduction: Heart transplantation is the only curative option available for patients with advanced heart failure. However, donor organ shortage and graft rejection remain critical challenges in heart transplantation. Blastocyst complementation using pluripotent stem cells (PSCs) can be used to generate organs such as the pancreas and kidneys in animal models with abnormalities in essential developmental genes. Nonetheless, whether functional adult hearts can be generated with blastocyst complementation remains unclear, and it is unknown if parenchyma, blood vessels, and stroma can be generated concomitantly from PSCs using blastocyst complementation to avoid graft rejection. Methods: We generated functional hearts in acardiac Mesp1 and Mesp2 double-knockout (Mesp1/2-DKO) mice via blastocyst complementation using mouse and rat PSCs. Results: The generated adult murine hearts were structurally and functionally normal and restored embryonic lethality in Mesp1/2-DKO mice. All four cardiovascular lineages, including cardiomyocytes, vascular endothelial cells, smooth muscle cells, and cardiac fibroblasts, were virtually entirely derived from exogenous PSCs in the myocardium. Exogenous rat PSCs also generated rat-derived xenogeneic hearts in Mesp1/2-DKO mice via interspecies blastocyst complementation. Conclusions: Blastocyst complementation is a viable technique for generating hearts derived from PSCs and may represent significant progress toward generating rejection-free hearts.
Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies
Authors: Dawn M.R. Davis, Aaron M. Drucker, Ali Alikhan, Lionel Bercovitch, David E. Cohen, Jennifer M. Darr, Lawrence F. Eichenfield, Lindsy Frazer-Green, Amy S. Paller, Kathryn Schwarzenberger, Jonathan I. Silverberg, Anne Marie Singh, Peggy A. Wu, Robert Sidbury
Journal: Journal of the American Academy of Dermatology (2023)
How do I cope with the menopause at work?
Authors: Éabha Lynn
Journal: BMJ (2023)

How do I cope with the menopause at work? Menopause can interfere with your working life but there are ways to make symptoms more manageable, Éabha Lynn hears Éabha LynnTalk to someone you trust Erin Duralde, medical director of women's health-clinical effectiveness, One Medical, says, "Menopause is a time of transition which can bring relief, comfort, and self-confidence to many, although it may also be marked by new bothersome symptoms, which can be severe and life altering."Recent studies have shown as many as 15% of women experiencing menopause report it impacts their ability to work, with many missing work and some quitting as a result. 1 Symptoms may begin as early as 10 years before your final menstrual period, and they may impact your ability to stay focused, confident, and comfortable at work.
A randomized phase III study of standard versus high-dose cytarabine with or without vorinostat for AML
Authors: Guillermo Garcia-Manero, Nikolai A Podoltsev, Megan Othus, John M Pagel, Jerald P Radich, Min Fang, David A Rizzieri, Guido Marcucci, Stephen A Strickland, Mark R Litzow, M Lynn Savoie, Bruno C Medeiros, Mikkael A Sekeres, Tara L Lin, Geoffrey L Uy, Bayard L Powell, Jonathan E Kolitz, Richard A Larson, Richard M Stone, David Claxton, James Essell, Selina M Luger, Sanjay R Mohan, Anna Moseley, Frederick R Appelbaum, Harry P Erba
Journal: Leukemia (2023)
Executive summary: Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies
Authors: Dawn M.R. Davis, Aaron M. Drucker, Ali Alikhan, Lionel Bercovitch, David E. Cohen, Jennifer M. Darr, Lawrence F. Eichenfield, Lindsy Frazer-Green, Amy S. Paller, Kathryn Schwarzenberger, Jonathan I. Silverberg, Anne Marie Singh, Peggy A. Wu, Robert Sidbury
Journal: Journal of the American Academy of Dermatology (2023)
Sacubitril/valsartan compared to ramipril in high‐risk post‐myocardial infarction patients stratified according to use of mineralocorticoid receptor antagonists: Insight from the <scp>PARADISE MI</scp> trial
Authors: Morten Schou, Brian Claggett, Zi Michael Miao, Alberto Fernandez, Gerasimos Filippatos, Christopher Granger, Karola Jering, Aldo P. Maggioni, Finnian McCausland, Julio Nuñez Villota, Jean‐Lucien Rouleau, Freny Vaghaiwalla Mody, Peter van der Meer, Dragos Vinereanu, Martina McGrath, Yinong Zhou, Douglas L. Mann, Scott D. Solomon, Philippe Gabriel Steg, Eugene Braunwald, John J.V. McMurray, Marc A. Pfeffer, Lars Køber
Journal: European Journal of Heart Failure (2023)
The correlation between gut microbiome and atrial fibrillation: pathophysiology and therapeutic perspectives
Authors: Na Li, Ling Wang, Lei Li, Meng-Zhao Yang, Qing-Xiang Wang, Xi-Wen Bai, Feng Gao, Yi-Qiang Yuan, Zu-Jiang Yu, Zhi-Gang Ren
Journal: Military Medical Research (2023)

Regulation of gut microbiota and its impact on human health is the theme of intensive research. The incidence and prevalence of atrial fibrillation (AF) are continuously escalating as the global population ages and chronic disease survival rates increase; however, the mechanisms are not entirely clarified. It is gaining awareness that alterations in the assembly, structure, and dynamics of gut microbiota are intimately engaged in the AF progression. Owing to advancements in next-generation sequencing technologies and computational strategies, researchers can explore novel linkages with the genomes, transcriptomes, proteomes, and metabolomes through parallel meta-omics approaches, rendering a panoramic view of the culture-independent microbial investigation. In this review, we summarized the evidence for a bidirectional correlation between AF and the gut microbiome. Furthermore, we proposed the concept of "gut-immune-heart" axis and addressed the direct and indirect causal roots between the gut microbiome and AF. The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions, which shed light on a definite direction for future experiments.
Ambient temperature and seasonal variation in inpatient mortality from respiratory diseases: a retrospective observational study
Authors: Hicham Achebak, Judith Garcia-Aymerich, Grégoire Rey, Zhaoyue Chen, Raúl Fernando Méndez-Turrubiates, Joan Ballester
Journal: The Lancet Regional Health - Europe (2023)

The seasonal fluctuation in mortality and hospital admissions from respiratory diseases, with a winter peak and a summer trough, is widely recognized in extratropical countries. However, little is known about the seasonality of inpatient mortality and the role of ambient temperature remains uncertain. We aimed to analyse the association between ambient temperature and in-hospital mortality from respiratory diseases in the provinces of Madrid and Barcelona, Spain.
The OX40-TRAF6 axis promotes CTLA-4 degradation to augment antitumor CD8+ T-cell immunity
Authors: Jizhang Yu, Jikai Cui, Xi Zhang, Heng Xu, Zhang Chen, Yuan Li, Yuqing Niu, Song Wang, Shuan Ran, Yanqiang Zou, Weicong Ye, Dan Zhang, Cheng Zhou, Jiahong Xia, Jie Wu
Journal: Cellular and Molecular Immunology (2023)
Mitochondrial DNA-triggered innate immune response: mechanisms and diseases
Authors: Ming-Ming Hu, Hong-Bing Shu
Journal: Cellular and Molecular Immunology (2023)

Abstract Various cellular stress conditions trigger mitochondrial DNA (mtDNA) release from mitochondria into the cytosol. The released mtDNA is sensed by the cGAS-MITA/STING pathway, resulting in the induced expression of type I interferon and other effector genes. These processes contribute to the innate immune response to viral infection and other stress factors. The deregulation of these processes causes autoimmune diseases, inflammatory metabolic disorders and cancer. Therefore, the cGAS-MITA/STING pathway is a potential target for intervention in infectious, inflammatory and autoimmune diseases as well as cancer. In this review, we focus on the mechanisms underlying the mtDNA-triggered activation of the cGAS-MITA/STING pathway, the effects of the pathway under various physiological and pathological conditions, and advances in the development of drugs that target cGAS and MITA/STING.
Public health approaches to gambling: a global review of legislative trends
Authors: Daria Ukhova, Virve Marionneau, Janne Nikkinen, Heather Wardle
Journal: The Lancet Public Health (2023)

The public health community has called for governments to recognise the harms associated with gambling, and for gambling policies to include population-based harm prevention approaches. This Health Policy explores the translation of this call into global policy action by systematically reviewing legislation of jurisdictions that introduced major gambling legislation change (ie, restricting or extending gambling provision) between Jan 1, 2018, and Dec 31, 2021. We mapped the global availability of legal gambling and changes in its provision, and conducted critical frame analysis on a sample of 33 jurisdictions introducing major policy change to assess the extent to which the protection of health and wellbeing was embedded within legislation. More than 80% of countries worldwide now legally permit gambling. Harmful gambling was recognised as a health and wellbeing issue in most of the analysed jurisdictions, but near-exclusive focus was given to individual-level harms rather than to wider social and economic harms, or harms to others. Most of the proposed prevention measures focused on individual responsibility. Gambling policies worldwide are changing, but addressing gambling as a public health issue is not yet translating into comprehensive policy action across jurisdictions.
Metformin attenuates mechanistic target of rapamycin complex 1/hypoxia-inducible factor-1α-driven glycolysis reducing keratinocyte and T helper 17 cell proliferation in hyperproliferative inflammatory skin diseases
Authors: Bodo C Melnik
Journal: British Journal of Dermatology (2023)

Journal Article Metformin attenuates mechanistic target of rapamycin complex 1/hypoxia-inducible factor-1α-driven glycolysis reducing keratinocyte and T helper 17 cell proliferation in hyperproliferative inflammatory skin diseases Get access Bodo C Melnik Bodo C Melnik Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany Email: melnik@t-online.de https://orcid.org/0000-0002-4501-1809 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 189, Issue 6, December 2023, Pages 652–653, https://doi.org/10.1093/bjd/ljad362 Published: 02 November 2023 Article history Received: 18 September 2023 Corrected and typeset: 02 November 2023 Published: 02 November 2023
Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD—a randomized controlled trial
Authors: Sadrija Cukoski, Christoph Heinrich Lindemann, Sita Arjune, Polina Todorova, Theresa Brecht, Adrian Kühn, Simon Oehm, Sebastian Strubl, Ingrid Becker, Ulrike Kämmerer, Jacob Alexander Torres, Franziska Meyer, Thomas Schömig, Nils Große Hokamp, Florian Siedek, Ingo Gottschalk, Thomas Benzing, Johannes Schmidt, Philipp Antczak, Thomas Weimbs, Franziska Grundmann, Roman-Ulrich Müller
Journal: Cell Reports Medicine (2023)

Ketogenic dietary interventions (KDIs) are beneficial in animal models of autosomal-dominant polycystic kidney disease (ADPKD). KETO-ADPKD, an exploratory, randomized, controlled trial, is intended to provide clinical translation of these findings (NCT04680780). Sixty-six patients were randomized to a KDI arm (ketogenic diet [KD] or water fasting [WF]) or the control group. Both interventions induce significant ketogenesis on the basis of blood and breath acetone measurements. Ninety-five percent (KD) and 85% (WF) report the diet as feasible. KD leads to significant reductions in body fat and liver volume. Additionally, KD is associated with reduced kidney volume (not reaching statistical significance). Interestingly, the KD group exhibits improved kidney function at the end of treatment, while the control and WF groups show a progressive decline, as is typical in ADPKD. Safety-relevant events are largely mild, expected (initial flu-like symptoms associated with KD), and transient. Safety assessment is complemented by nuclear magnetic resonance (NMR) lipid profile analyses.